Teratogenicity of antiepileptic drugs: role of pharmacogenomics.
The teratogenic potential of an antiepileptic drug is determined by the chemical attributes of the molecule under discussion and the genetic attributes of the host. The role of the hepatic mixed function oxidase system may be especially important in conferring teratogenic risk. However, systems such as epoxide hydrolase, glutathione reductase, and superoxide dismutase and other toxin scavenging systems may be important modifiers that lower the risk. Genetic variability in these systems is important in determining the type and severity of the final outcome. While our knowledge of these factors is incomplete, progress can be achieved by beginning to include these concepts in our discussion on the topic and by promoting research that may improve our ability to individualize the analysis of risk for a specific patient with regard to specific antiepileptic drugs. Such an approach will most likely involve DNA microchip technology and has the potential to overcome some of the limitations of pregnancy registries. Such an approach may also lead to novel interventions and therapeutics design to lower the teratogenic potential of pharmacologic treatment of epilepsy during conception.
Sankar
Raman
R
David Geffen School of Medicine at UCLA, Mattel Children's Hospital at UCLA, Los Angeles, California 90095-1752, USA.
Lerner
Jason T
JT
D000014:Abnormalities, Drug-Induced / Q000209:etiology* / Q000235:genetics*; D000927:Anticonvulsants / Q000009:adverse effects*; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D010597:Pharmacogenetics; D011247:Pregnancy; D011248:Pregnancy Complications
D000927:Anticonvulsants